Differences in effects of insulin glargine or pioglitazone added to oral anti-diabetic therapy in patients with type 2 diabetes: what to add--insulin glargine or pioglitazone?
BACKGROUND
While metformin is the first line treatment in type 2 diabetes, the best way to escalate therapy is not always clear, particularly whether to add one or two oral agents or to introduce insulin.


METHODS
Thirty-six patients inadequately controlled on metformin and sulfonylurea/meglitinide were randomized to receive add-on therapy with insulin glargine or pioglitazone for 26 weeks. Insulin was up-titrated to achieve fasting plasma glucose <6 mmol/l. Pioglitazone was increased to 45 mg/day after 16 weeks if HbA1c>6.2%. beta-Cell function and insulin sensitivity were assessed by measuring insulin, proinsulin and adiponectin, and in a subgroup using a combined glucagon-stimulated C-peptide test and insulin tolerance test (GITT). Lipids and natriuretic peptides were measured at start and end of study.


RESULTS
The reduction in HbA1c was slightly greater in the insulin glargine group and used as co-variate when analysing other variables. The effect on beta-cell function was more favourable with insulin glargine measured by proinsulin (42+/-48 to 19+/-16, p=0.01 vs. 36+/-26 to 27+/-16 p=0.04) while the improvement in insulin sensitivity measured by adiponectin (7.5+/-3.7 to 15+/-10, p<0.01 vs. 8.7+/-4 to 7.6+/-3, p=0.04) and HDL cholesterol (1.10+/-0.24 to 1.24+/-0.3, p<0.01 vs. 1.08+/-0.35 to 1.04+/-0.33, ns) (all p between groups <0.01) was more favourable in pioglitazone group. Pioglitazone caused significant increase in natriuretic peptides (BNP pmol/l 6.6+/-5.2 to 13.7+/-16.1, p=0.04 vs. 8.8+/-11.6 to 8.6+/-10.6, ns, p between groups 0.028).


CONCLUSIONS
The results demonstrate characteristic differences in the effects of insulin glargine vs. pioglitazone on measures of beta-cell function and insulin sensitivity as well as cardiac load.
Dorkhan
Mozhgan
M
Department of Clinical Sciences, Division of Diabetes & Endocrinology, Lund University, Malmö University Hospital, Malmö S-20502, Sweden. mozhgan.dorkhan@med.lu.se
Frid
Anders
A
Groop
Leif
L
D052242:Adiponectin / Q000097:blood; D000328:Adult; D000368:Aged; D001549:Benzamides / Q000627:therapeutic use; D003924:Diabetes Mellitus, Type 2 / Q000188:drug therapy*; D004359:Drug Therapy, Combination; D006442:Glycated Hemoglobin / Q000032:analysis; D006334:Heart Function Tests; D006801:Humans; D007004:Hypoglycemic Agents / Q000008:administration & dosage*; D007328:Insulin / Q000008:administration & dosage / Q000031:analogs & derivatives*; D000069036:Insulin Glargine; D007333:Insulin Resistance; D049528:Insulin, Long-Acting; D008687:Metformin / Q000627:therapeutic use; D008875:Middle Aged; D000077205:Pioglitazone; D011384:Proinsulin / Q000097:blood; D013453:Sulfonylurea Compounds / Q000627:therapeutic use; D045162:Thiazolidinediones / Q000008:administration & dosage*; D016896:Treatment Outcome; D055815:Young Adult
D052242:Adiponectin; D001549:Benzamides; D006442:Glycated Hemoglobin; D007004:Hypoglycemic Agents; D007328:Insulin; D000069036:Insulin Glargine; D049528:Insulin, Long-Acting; D008687:Metformin; D000077205:Pioglitazone; D011384:Proinsulin; D013453:Sulfonylurea Compounds; D045162:Thiazolidinediones; C030516:meglitinide